tbuckley/cabot-search huggingface dataset:
ATRT-09. Outcome and therapeutic interventions in relapsed and refractory ATRT – The EU-RHAB perspective
Authors: Mona Steinbügl, Karolina Nemes, Miriam Gruhle, Pascal Johann, Maria Joao Gil-da-Costa, Martin Ebinger, Astrid Sehested, Peter Hauser, Harald Reinhard, Simone Hettmer, Marcus Jakob, Stefan Rutkowski, Pablo Hernáiz Driever, Gudrun Fleischhack, Kornelius Kerl, Olaf Witt, Joachim Gerss, Reiner Siebert, Ulrich Schüller, Martin Hasselblatt, Michael C Frühwald
Journal: Neuro-Oncology (2022)

Abstract Currently an internationally accepted consensus treatment for relapsed/refractory ATRT is missing. Little is known about relapse patterns, prognostic factors and outcome. In a recently published cohort of 143 ATRTs from the EU-RHAB registry, progression on therapy or relapse occurred in 64% (n=91). Previously published strategies for treatment failure have been restricted to individual, mostly clinically guided, attempts or early phase trials with limited sample sizes. We present a cohort of 55 patients with relapsed/refractory ATRT identified between 2015 and 2021 (total ATRT recruited n=147). Median age was 19 months; in 27.3% (n=15) a germline mutation was identified. A total of 43/55 tumors were subgrouped [60.5% SHH (n=26), 14.0% MYC (n=6), 23.3% TYR (n=10), one patient with SHH+TYR]. Salvage therapy was applied to 83.6% (46/55). Sixty therapy attempts with 17 different regimens subclassified into conventional chemotherapy, epigenetic, targeted or metronomic therapy were applied to 40/55 patients. Median overall survival (OS) was 20±1.8 weeks following the first event, median time to progression was 11±1.8 weeks. 12 months OS was 23.1%. No significant differences in survival were noted between different molecular subgroups; neither was germline mutation in SMARCB1 prognostic. Patients &amp;lt;12 months (n=9;16.4%) had a significantly reduced OS compared to older patients. (9±6.0wks vs. 22±3.2wks, p&amp;lt;0.05) Those who received therapy according to metronomic approaches such as MEMMAT (8/55;14.5%) survived longer than patients treated with other regimens, including epigenetic and targeted therapy. (72±36.8wks vs. 25±6.2wks, p&amp;lt;0.05) Our data provide valuable insights into a vulnerable group of patients deserving evidence based clinical management and access to clinical trials of all phases. Prospectively we aim to merge the results with data from other, international cohorts to generate more robust and valuable results.
The kinetic mechanism of cations induced protein nanotubes self-assembly and their application as delivery system
Authors: Jipeng Zhang, Qimeng Wang, Bin Liu, Dan Li, Huijuan Zhang, Pengjie Wang, Jinfang Liu, Guohua Hou, Xin Li, Yu Yuan, Zekun Li, Shanan Chen, Huiling Yan, Yuan Li
Journal: Biomaterials (2022)
ATRT-18. Atypical Teratoid/Rhabdoid Tumor in Children: Case Reports from Indonesia
Authors: Diko Anugrah Ramadhan, Wanda Gautami, Ludi Dhyani Rahmartani, Ahmad Rafli, Kevin Gunawan, Mohamad Yanuar Amal, Eka Susanto, Handoko Handoko
Journal: Neuro-Oncology (2022)

Abstract Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a sporadic and highly malignant tumor that usually affects very young children and is typically deadly despite very aggressive treatment. The optimal treatment for AT/RT remains unclear, including surgery, radiotherapy, and chemotherapy. Here we report cases of AT/RT in Indonesia. Case 1: A three-year-old girl came with worsening intermittent headaches with projectile vomiting, progressive and insidious right spastic hemiparesis, and slowly progressive weight loss three months before admission. She had septate multiloculated hydrocephalus. Head MRI demonstrates a solid lobulated mass with heterogeneous enhancement and MRS shows an aggressive metabolite pattern, arising from posterior fossa extending into the cerebellum and cerebellopontine angle, causing severe obstructive hydrocephalus. She underwent tumor resection with a midline suboccipital approach, then continued with craniospinal irradiation with dose of 36 Gy in 20 fractions then followed by 18 Gy in 10 fractions booster to posterior fossa, making the total dose to posterior fossa (the tumor) to be 54 Gy. Case 2: A twenty-month-old baby with a history of recurrent seizures, tremors, and less activity in the last two months. She had spasticity with hyperreflexia. She has been referred to our center for further evaluation and management after biopsy and VP shunt surgery at the previous hospital. Head CT scan demonstrates a large solid heterogeneous mass in the right hemisphere cerebral, causing midline shift and hydrocephalus. After the VP shunt was repaired, she underwent Head Start III chemotherapy protocol cycle 1. Both pathology examinations of the patients revealed a hypercellular tumor with prominent hyperchromatic nucleoli and loss of INI-1 staining on immunohistochemistry consistent with an ATRT diagnosis. Unfortunately, both patients died due to severe sepsis after treatment. Although AT/RT has become increasingly recognized, prognosis of ATRT is generally unfavorable, especially in developing countries.
Adapting an evidence-based cancer survivor lifestyle program for cancer prevention and control in African American and Hispanic/Latino communities.
Authors: Jamila L. Kwarteng, Laura Pinsoneault, AnaKaren Manriquez Prado, Sophia Aboagye, Sandra Contreras, Erica Wasserman, Derek Donlevy, Patricia M. Sheean, Margaret Tovar, Regina Vidaver, Sailaja Kamaraju, Melinda Stolley
Journal: Journal of Clinical Oncology (2022)

10545 Background: Cancer is the second leading cause of death in Wisconsin with higher mortality rates observed for Black/African American (B/AA) and Hispanic/Latino(a) (Hisp/Lat) communities. Affordable lifestyle interventions targeting healthy nutrition and physical activity patterns tailored to the needs/interests of these communities are critically needed to prevent and control cancer. In this project, we adapted the evidence-based Moving Forward lifestyle program for B/AA breast cancer survivors, which included a program workbook, in-person education/supervised exercise classes, and text messages. We sought to address cancer prevention among B/AA and Hisp/Lat community members in the general population by implementing the program within an urban public recreation system for sustainability. Methods: To help guide the adaptation process, project partners included an academic cancer center, an urban public recreation system, the state department of public health, and a community advisory board. Our approach comprised of focus groups with B/AA and Hisp/Lat residents, surveys collected at community events, and an After-Action Review of a 4-week program pilot. Results: One-hundred community members (58 B/AA and 42 Hisp/Lat) participated in the adaptation phase through eight focus groups (N = 27), 48 surveys, and 25 pilot participants. Seven key program content adaptations were targeted: 1) integrate information on basic cancer biology; 2) explain the association between cancer, nutrition and physical activity; 3) address other diseases besides cancer (heart disease, diabetes); 4) provide cooking demonstrations with culturally relevant tips to facilitate dietary changes; 5) update workbook images and content to reflect race/ethnicity of targeted populations; 6) add information on cancer screening; 7) provide information on local healthy eating and exercise resources. Key adaptations related to conducting the program within a public recreation system included: 1) dividing the program into two 8-week sessions to meet the public recreation system program calendar; 2) eliminating the text message component; 3) providing the program workbook/classes in English and Spanish; and 4) integrating different exercise approaches to meet needs/interests of different age groups, genders, and different fitness levels. Conclusions: Community-academic partnerships and ongoing community engagement led to meaningful adaptations to a cancer prevention and lifestyle program to address cancer disparities in the B/AA and Hisp/Lat communities.
Combined assessment of metabolic response and tumor infiltrating lymphocytes as a predictor of outcomes following neoadjuvant therapy for HER2-positive breast cancer: Results from the randomized PREDIX HER2 trial.
Authors: Alexios Matikas, Hemming Johansson, Per Grybäck, Judith Bjöhle, Tobias Lekberg, Hanna Fredholm, Balazs Acs, Ellinor Elinder, Erika Isaksson-Friman, Susanne Agartz, Mats Hellstrom, Ioannis Zerdes, Johan Hartman, Jonas C. S. Bergh, Thomas Hatschek, Theodoros Foukakis
Journal: Journal of Clinical Oncology (2022)

593 Background: Abundance of tumor infiltrating lymphocytes (TIL) is prognostic in early HER2-positive breast cancer (BC). Response to neoadjuvant therapy (NAT) according to positron emission tomography combined with computed tomography (PET-CT) has been shown to predict pathologic complete response (pCR). There is paucity of data regarding long-term prognostication using PET-CT and the potential value of the combined assessment of both these biomarkers. Methods: PREDIX HER2 (NCT02568839) is a prospective randomized phase 2 trial that compared standard NAT (docetaxel, trastuzumab, pertuzumab) with trastuzumab emtansine, in patients with HER2-positive BC. Overall, 202 patients were included (197 evaluable) and the primary efficacy analysis showed no difference in pCR or event-free survival (EFS) between the two groups (Hatschek, JAMA Oncology 2021). Assessment with fluorine 18–labeled fluorodeoxyglucose PET-CT was performed at baseline and after 2 and 6 treatment cycles, and SUVmax was evaluated as a continuous variable. TILs were assessed at baseline biopsies according to guidelines from the International TIL Working Group (J.H.). The aim of this secondary analysis was to investigate the combined assessment of TIL and PET-CT as an early predictor of response to NAT. Results: Overall, 112 patients underwent baseline PET-CT and 109 after C2, whereas 173 had baseline TIL. In multivariable analysis, baseline SUVmax did not predict pCR (OR adj = 1.04, 95% CI 0.97-1.12, p = 0.259) or EFS (HR adj = 1.07, 95% CI 0.98-1.17, p = 0.117). In contrast, higher SUVmax at C2 predicted lower pCR (OR adj = 0.65, 95% CI 0.48-0.87, p = 0.005) and worse EFS (HR adj = 1.18, 95% CI 1.04-1.34, p = 0.01). Baseline TIL &gt; 10% (median cut-off) provided additional prognostic information to clinical parameters (stage and hormone receptor expression) and C2 SUVmax (LR-Δχ 2 = 7.19, p = 0.007; OR adj = 3.52, 95% CI 1.37 – 9.06, p = 0.009). 75% of patients with high TIL and C2 SUVmax &lt; 2.49 achieved pCR, compared with 13.8% of those with low TIL and high C2 SUVmax and 39.1%-41.3% for the intermediate groups (p = 0.001). Conclusions: SUVmax after two cycles of NAT for HER2-positive BC is an independent predictor of both short- and long-term outcomes. A combined assessment with TIL may facilitate early selection of good responders for de-escalation and poor responders for alternative treatment strategies. Clinical trial information: NCT02568839.
Racial and regional disparities in metastatic breast cancer.
Authors: Sachi Singhal, Devashish Desai, Akshita Khosla, Oladimeji Lanade, Rashmika Potdar
Journal: Journal of Clinical Oncology (2022)

10516 Background: Breast cancer is the most commonly diagnosed malignancy in American women, with about 281,500 new reported cases this year, 3.8 million women living with an active or history of breast cancer, and a lifetime occurrence of 1 in 8 women in this nation. Racial disparities persist despite the advent and implementation of screening by national agencies. AA females are less likely to be diagnosed with breast cancer, and yet bear an arbitrarily high burden of mortality of this malignancy. Socioeconomic variables and lifestyle are the most plausible explanations of this discrepancy. Even in clinical trials, there remains an underrepresentation of all ethnic minorities. Encouragement of guideline based screening for all along with constant follow ups, access to health insurance and a more uniform representation in trials are the cornerstone of eliminating these disparities. Methods: Data for this study was obtained from the 2016-18 Nationwide Inpatient Sample (NIS) which comprises 20% of the total US hospital discharges. We identified all patients with a primary diagnosis of Malignant Neoplasms of Breast. In-hospital mortality, race and hospital regions for the given patients were studied. Baseline characteristics of participants were summarized using descriptive statistics. The patient population was stratified as per race, hospital region, gender, therapy they received and family history. Logistic regression was performed to derive the odds ratio while adjusting for different variables. Further details: https://www.hcup-us.ahrq.gov/ . Results: 99, 543 patients with metastatic breast cancer were identified, and almost 99% of them were females. 67% of the population was comprised of Caucasians, 16.91% African Americans (AA), 9.14% Hispanics and 3.28% Asians and Pacific Islanders (API). AAs had the most reported deaths at 5.54%, followed by APIs at 4.80% and Caucasians 4.09% (p &lt; 0.0001). The odds of dying were significantly higher in AA population when compared to Caucasian population (OR 1.391 (1.286-1.504)), and the odds were consistently higher across all regions of the US. In terms of regional variation, it was seen that races identifying as “others' ' had significantly higher odds of dying in the North East (OR 1.646 (1.238-2.189)) and the West (OR 1.503 (1.059-2.133)). Conclusions: It is crucial to identify racial disparities in diagnosis, treatment and mortality before we devise a blueprint to tackle this incongruity. This highlights the significance of universal screening and better health insurance coverage in addition to recognition of reasons behind these differences.
The Breast Cancer Index Registry Study: Initial analysis of the first 1,000 patients.
Authors: Joyce O'Shaughnessy, Carlos A. Encarnacion, Brandon O'Neal, Jenna Wong, Natalia Siuliukina, Tara B. Sanft, Rachel Catherine Jankowitz, Mark D. Pegram, Kai Treuner, Jenny R. Fox
Journal: Journal of Clinical Oncology (2022)

e12513 Background: The Breast Cancer Index (BCI) is a gene expression-based biomarker that reports two results: BCI Predictive [BCI (H/I)], which predicts benefit from extended endocrine therapy (EET), and BCI Prognostic, which combines the Molecular Grade Index (MGI) with BCI (H/I) to provide individualized risk of both late (5-10 years) and overall (0-10 years) distant recurrence. The NCCN clinical practice guideline recommends use of BCI for prediction of benefit from EET in early stage, hormone receptor positive (HR+) breast cancer patients. Methods: The BCI Registry study was designed to prospectively evaluate the long-term clinical outcome, medication adherence and quality of life in HR+ early-stage breast cancer patients receiving BCI testing as part of routine clinical care. The BCI registry will enroll approximately 3,000 patients after completion of 4-7 years of primary adjuvant endocrine therapy. Patients will be followed for disease recurrence for at least 10 years from diagnosis. Patients extending endocrine therapy will be assessed annually for medication adherence. To evaluate the impact of BCI results on EET decision making, both the physician and patient will complete Decision Impact Questionnaires. Clinicopathological data are collected within the ClinCapture electronic data capture system. The BCI Registry Study is registered on ClinicalTrials.gov under NCT04875351. Results: The BCI Registry Study completed enrollment of the first 1,000 patients in January 2022. Clinical data were available for 942 patients (76.8% T1; 51.3% grade II; 75.4% N0). BCI test results were reported for 842 patients. 315 patients (37.4%) were classified as BCI (H/I)-High and 527 patients (62.6%) as BCI (H/I)-Low. Further, in node-negative (N0) patients, BCI classified 314 N0 patients (47.9%) with high risk for late distant recurrence and 342 patients (52.1%) with low risk. In node-positive (N1) patients, BCI classified 138 patients (74.2%) as high risk for late distant recurrence and 48 patients (25.8%) as low risk. The associated clinicopathological factors are shown in the table. Conclusions: The analysis of the first 1,000 BCI Registry patients confirms the expected distribution of clinicopathological factors. BCI by H/I status and prognostic risk groups are consistent with previous clinical validation studies. Clinical trial information: NCT04875351. [Table: see text]
Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease
Authors: Arce Domingo-Relloso, Kiran Makhani, Angela L. Riffo-Campos, Maria Tellez-Plaza, Kathleen Oros Klein, Pooja Subedi, Jinying Zhao, Katherine A. Moon, Anne K. Bozack, Karin Haack, Walter Goessler, Jason G. Umans, Lyle G. Best, Ying Zhang, Miguel Herreros-Martinez, Ronald A. Glabonjat, Kathrin Schilling, Marta Galvez-Fernandez, Jack W. Kent, Tiffany R Sanchez, Kent D. Taylor, W. Craig Johnson, Peter Durda, Russell P. Tracy, Jerome I. Rotter, Stephen S. Rich, David Van Den Berg, Silva Kasela, Tuuli Lappalainen, Ramachandran S Vasan, Roby Joehanes, Barbara V. Howard, Daniel Levy, Kurt Lohman, Yongmei Liu, M Daniele Fallin, Shelley A. Cole, Koren K. Mann, Ana Navas-Acien
Journal: Circulation Research (2022)

Background: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD. Methods: Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Strong Heart Study, a prospective cohort of American Indians. Urinary arsenic species were measured using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. We identified DMPs that are potential mediators between arsenic and CVD. In a cross-species analysis, we compared those DMPs with differential liver DNA methylation following early-life arsenic exposure in the apoE knockout (apoE −/− ) mouse model of atherosclerosis. Results: A total of 20 and 13 DMPs were potential mediators for CVD incidence and mortality, respectively, several of them annotated to genes related to diabetes. Eleven of these DMPs were similarly associated with incident CVD in 3 diverse prospective cohorts (Framingham Heart Study, Women’s Health Initiative, and Multi-Ethnic Study of Atherosclerosis). In the mouse model, differentially methylated regions in 20 of those genes and DMPs in 10 genes were associated with arsenic. Conclusions: Differential DNA methylation might be part of the biological link between arsenic and CVD. The gene functions suggest that diabetes might represent a relevant mechanism for arsenic-related cardiovascular risk in populations with a high burden of diabetes.
Predictors of phosphodiesterase type 5 Inhibitors (PDE5I)-discontinuation – Is a previous PDE5I-exposure at first clinical evaluation related with a higher PDE5I-drop-out risk?
Authors: N. Schifano, P. Capogrosso, G. Fallara, E. Pozzi, F. Belladelli, L. Candela, C. Corsini, M. Raffo, A. Costa, D. Cignoli, A. D'Arma, L. Boeri, E. Ventimiglia, R. Matloob, V. Mirone, F. Deho', F. Montorsi, A. Salonia
Journal: European Urology (2022)
Application of value framework to phase III trials of immune checkpoint inhibitors in esophageal and gastric cancer.
Authors: Rajat Thawani, Neha Agrawal, Nicholas Taflin, Adel Kardosh, Emerson Yu-sheng Chen
Journal: Journal of Clinical Oncology (2022)

e18817 Background: Recent clinical trials testing use of immune-checkpoint inhibitors in esophageal and gastric carcinomas have shown both positive and negative results. Given these mixed signals, we aimed to assess outcomes and tolerability of key subgroups using the ASCO Net Health Benefit Score (NHBS) and ESMO Magnitude of Clinical Benefit Scale (MCBS). Methods: A detailed search for phase III trials investigating use of FDA-approved anti PD-1 or anti PD-L1 drugs in esophageal and gastric cancer trials was completed using www.clinicaltrials.gov followed by primary literature identification on PubMed. These studies were then independently selected, reviewed, and scored using the ASCO NHBS and ESMO MCBS by two investigators, and any discrepancy was mutually resolved. The ASCO NGBS scores were compared by primary site of cancer (esophageal vs gastric) and PD-L1 expression using the Mann-Whitney test. The ESMO-MCBS grading were compared using Fisher's Exact test. Results: Of the 45 records identified, 15 clinical trials were included. Of them, six were primarily esophageal cancer trials, and nine were primarily gastric cancer trials. Of all 15, 10 stratified their analysis based on PD-L1 expression. The ASCO NHBS score was significantly higher for esophageal cancer than gastric cancer (mean 40, range 20  56.6 vs. mean 12, range -1.1  18.4, p &lt; .01). No difference, however, was observed in survival and response rate outcome endpoints between the two groups. Similarly, the ESMO MCBS was also higher for esophageal cancer group than gastric cancer (p &lt; .05). Additionally, the median scores were higher in the patients with high PD-L1 expression vs low PD-L1 expression (mean 37, range 11.2  66.6 vs. mean 14, range -19.5  43.6, p &lt; .05). Conclusions: In this cohort of drug registration trials of immune checkpoint inhibitors for upper GI cancers, we showed the ASCO NHB scores and ESMO scores were consistently higher among esophageal cancer trials than gastric cancer trials and in those with high PD-L1 expression than those with low PD-L1 expression. Oncologists should carefully discuss overall clinical value and expectations of immunotherapy benefit with their patients per cancer histology and PDL1 expression, exercising caution in cases of gastric adenocarcinoma with low PD-L1 expression.[Table: see text]